Monday, 22 October 2012

Pancreatic extracts in the treatment of diabetes mellitus - classic paper

We've been having a 'extra-curricular' discussion on historical aspects of diabetes on the Postgraduate Diploma course.

I just found this open access copy of the full text of the classic paper from 1922 and thought I'd share it.

It describes the very first cases (seven to the date of the article) of the use of insulin in the treatment of people with Type 1 Diabetes. Reading it makes you relive the palpable excitement of the discovery. Classic.
"Patients report a complete relief from the subjective symptoms of the disease. The sugar excretion shows marked decrease or, if dosage be adequate, disappears. Ketonuria is abolished, thus confirming a similar observation by Collip in diabetic animals (results as yet unpublished)."
Banting FG, Best CH, Collip JB, Campell WR, Fletcher AA (1922). Pancreatic extracts in the treatment of diabetes mellitus. Canadian Medical Association Journal 12: 141 - 146.

iGel supraglottic airway for resuscitation

I had mandatory training at my NHS Trust last week and got to play with quite marvellous device - the iGel supraglottic airway.

OK it probably shows how little acute medicine I do but this was a much better experience than the usual 'tooth cracking' struggle with an ET tube.

On the manikin at least it seemed quite straight forward to get a secure airway sufficient for CPR.

The device is used as an initial airway choice in resuscitation and a case series from Gloucester of 100 resuscitations gives some evidence of its effectiveness in practice [1]. This is the practice in our hospital and the anaesthetist then makes the decision on what to use for airways management when they arrive at the crash call.

I wouldn't be confident about its ability to prevent aspiration but it is clearly more useful for airway control by novices until someone experienced at endotracheal intubation arrives.

1. Larkin C, King B, D’Agapeyeff A, Gabbott D. iGel supraglottic airway use during hospital cardiopulmonary resuscitation. Resuscitation 2012 Jun;83(6):e141. Available from:

Saturday, 13 October 2012

Do you want a reprint with that? My 'bad pharma Friday'.

"Yes", I said, vaguely remembering the debate on aldosterone antagonists from a couple of years ago but not being able to recall exactly what it was all about.

We had a presentation in the hospital from a Pfizer rep on their drug eplerenone (Inspra) and it went through the results of the EMPHASIS-HF trial [1] talking about how that  has affected the European Society of Cardiology guidelines for heart failure and how the local cardiologists apparently 'use it anyway'.

A reprint of the EMPHASIS-HF trial was offered and I then saw that, yes, it was a Pfizer-sponsored trial of eplerenone against placebo. Also, it did not include the accompanying editorial in the same issue of the NEJM by Paul Amstrong.

There are two issues here:
  • Selective reporting of evidence. It was not made clear that the major change to the guidelines was in the placement of mineralocorticoid antagonists (spironolactone AND eplerenone) ahead of ARBs which state: "ARBs are no longer the first choice recommendation in patients with HF and an EF ≤40% who remain symptomatic despite optimal treatment with an ACE inhibitor and beta-blocker. This is because in EMPHASIS-HF, eplerenone led to a larger reduction in morbidity–mortality than seen in the ARB ‘add-on’ trials discussed below, and because in both the Randomized Aldactone Evaluation Study (RALES) and EMPHASIS-HF, MRA treatment reduced all-cause mortality, whereas ARB 'add-on' treatment did not.". The RALES trial showed the benefits of spironolactone in a similar group of patients [2].
  • Selective reporting of opinion. The editorial commentary which suggested that the more expensive eplerenone should be reserved for those who do not tolerate spironolactone was not addressed. Notice also how the Pfizer-sponsored trial is freely available on NEJM but the accompanying editorial is not. Shame on you NEJM. Freely available copies of the editorial are available here, and here. Other commentators agree. As our National Prescribing Centre (NICE) points out "the results are consistent with those seen with spironolactone in the RALES study".
Now I'm no cardiologist and I haven't ever prescribed eplerenone but, to me, my 'bad pharma Friday' looked like a bit of a demonstration of nice outcomes data of a slightly better tolerated but patented expensive drug versus placebo whilst hiding the real debate about its position in the treatment algorithms compared with another effective, off-patent, much cheaper drug.

Time to read my Kindle copy of Ben Goldacre's new book 'Bad Pharma' I think.

1. Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B. Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 2011 Jan;364(1):11–21.

2. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 1999 Sep;341(10):709–717.